L-Glutamate (as in monosodium glutamate, MSG) is an important free amino acid constituent of many foodstuffs. Many researchers believe the taste of MSG differs fundamentally from sweet, sour, salty, and bitter MSG elicits a complex taste that has been umami. MSG stimulates food intake in humans and animals alike. In taste buds, transduction for MSG appears to be distinct from other taste qualities. As described in the Overview, we hypothesize that taste bud cells transduce this amino acid via apical receptors similar to glutamate receptors found in the brain. More specifically, we postulate that a metabotropic glutamate receptor similar to mGluR4 a G protein-coupled receptor found at synapses in the brain is central in MS taste transduction. During the current funding period, we discovered that rat taste bud cells express a unique variant of mGluR4 and that stimulation of this novel receptor appears to mimic aspects of glutamate taste. In addition, however, other glutamate receptors may be present in taste bud cells and participate in glutamate taste transduction. Conceivably, glutamate activates multiple receptor mechanisms in taste bud cells. Thus, a complete explanation of MSG taste transduction may involve more than one receptor mechanism. Indeed, this notion forms the working hypothesis for our study. The intent of the studies proposed in Project #2 is twofold. First, the experiments will provide morphological correlates for the molecular and functional studies described in Projects 1 and 3. That is, we will use in situ hybridization and immunocytochemistry to visualize glutamate receptors in taste buds. Second, the experiments will extend the analyses being conducted at the molecular and membrane levels to the level of sensory afferent fibers and ultimately animal behavioral responses. We will collaborate with two leading laboratories in the fields of chemical senses and animal behavior to record responses from single gustatory afferent fibers and to conduct detailed taste synergy and taste discrimination studies. By combining a multi-disciplinary approach at several levels of analysis, we hope to contribute significantly to an understanding of how taste bud cells transduce MSG taste.